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Study Summary
No. 2005-0366:.......Blood And Marrow Transplantation; Leukemia......Richard E. Champlin......Stem Cell Transplantation and Cellular Therapy
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Study Summary Title
Study Summary
Number:
2005-0366
Study Title:A randomized study of once daily IV Busulfan with Fludarabine with hemopoietic stem cell transplantation for AML and MDS
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Physician New Patient Referral
Name:Richard E. ChamplinPatients Call:800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)
Dept:Stem Cell Transplantation and Cellular TherapyReferring MD
Call:
800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)
Phone:713-792-8750
Contact us about clinical trials
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General Information
Disease Group:Blood And Marrow Transplantation
Leukemia
Supported By:N/A
Phase of Study:Phase IIIReturn
Visit:
up to daily for the first 100 days, every 3 months for one year, yearly
thereafter x 5 years
Treatment
Agents:
Antithymocyte Globulin
Busulfan
Fludarabine
Home Care:none
Treatment Loc:Only at MDACC
Estimated
Length of Stay
in Houston:
28 days
Description/
Intervention:
The goal of this clinical research study is to learn if giving busulfan in a
dose based on blood levels, along with a fixed (unchanging) dose of
fludarabine, is more effective and causes fewer side effects for AML or
myelodysplastic syndrome patients than the standard method of giving a fixed
busulfan dose based on body size, along with a fixed dose of fludarabine. The
safety of dosing based on blood levels will also be studied.
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Study Objectives / Outcomes
1. To determine if busulfan (Bu) given in pharmacokinetically adjusted dose to yield a blood daily AUC of 6,000 microMol-min is superior to a fixed dose of 130 mg/m2 to prevent treatment failure (relapse or death from any cause) in patients with acute myelogenous leukemia and myelodysplastic syndrome. This dose will be given intravenously over three hours once daily for four (4) days, each dose preceded by Fludarabine at a dose of 40 mg/m2, as preparation for bone marrow or peripheral blood progenitor cell transplantation.
      2. To determine the outcomes of AML/MDS patients undergoing treatment
        with this regimen. Data regarding engraftment, toxicity, relapse rate, long-term overall and disease-free survival will be collected.

      3. To describe the plasma pharmacokinetics of busulfan when administered intravenously in this regimen.
      4. To determine if the uniformly delivered variant of the Busulfan-Fludarabine regimen (daily AUC approximately 6,000 microMol-min ±10%) will confer a survival advantage compared with the fixed-dose delivery regimen (daily AUC approximately 5,000 microMol-min, range 3,500-7,500).
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    Study Status Information
    Study Activation / Registration Date:06/28/2005
    IRB Review and Approval Date:06/15/2005
    Study Type:Therapeutic
    Recruitment Status:Open
    Projected Accrual:N/A
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    Enrollment Eligibility
    If you do not meet the enrollment eligibility, there may be other treatment options for you. Please Contact the Referral Office for more information.

    Inclusion Criteria:1) Acute myeloid leukemia past first remission, in first or subsequent relapse, in first remission (cytogenetics other than t(8;21, inv 16, t(15;17)) or induction failures. Only myeloid leukemia but not biphenotypic leukemia is allowed on this study.

    2) Myelodysplastic syndromes with intermediate or high risk International Prognostic Scoring System score

    3) Patient has not been administered any other systemic chemotherapeutic drug (including Mylotarg) within 21 days prior to trial enrollment (BMT Day –7 or day –9 for the test-dose arm of the study). Hydroxyurea is permitted if indicated to control induction refractory disease, and IT chemotherapy is allowed if indicated as maintenance treatment for previously diagnosed leptomeningeal disease, that has been in remission for at least 3 months prior to enrollment on this study).

    4) No active infection. Protocol PI will be final arbiter if there is uncertainty regarding whether a previous infection is resolved.

    5) age <=65

    6) Patients must have a matched related or unrelated donor willing to donate. A donor who is HLA identical or mismatched in 1 locus on Class I [HLA, A or B], or molecularly mismatched in 1 locus on Class II [HLA, DR or DQ] is also acceptable.

    7) ZUBROD performance status <2

    8) Life expectancy is not severely limited by concomitant illness and expected to be >12 weeks.

    9) Left ventricular ejection fraction >45% No uncontrolled arrhythmias or symptomatic cardiac disease.

    10) No symptomatic pulmonary disease. FEV1, FVC and DLCO >/= 50% of expected corrected for hemoglobin. In patients </= 7 years pulmonary function will be assessed per pediatric BMT routine

    11) Serum creatinine </= 1.5 mg%.

    12) SGPT </= 200 IU/ml, serum bilirubin and alkaline phosphatase within accepted laboratory standard normal limits or considered not clinically significant. No evidence of chronic active hepatitis or cirrhosis. If positive hepatitis serology, discuss with Study Chairman and consider liver biopsy.

    13) No effusion or ascites >1L prior to drainage.

    14) HIV-negative.

    15) Female patient is not pregnant (negative B-HCG pregnancy test in all women of child-bearing-potential in accordance with departmental routine).

    16) Patient or patient's legal representative, parent(s) or guardian able to sign informed consent.

    17) No prior autologous stem cell transplants

    Exclusion Criteria:N/A

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    Links
    Registration Number: NCT00469144
    Study Information on Clinical Trials Registry (clinicaltrials.gov)

    Other Links:
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    Results


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